PUBLICATION
UV radiation promotes melanoma dissemination mediated by the sequential reaction axis of cathepsins-TGF-β1-FAP-α
- Authors
- Wäster, P., Orfanidis, K., Eriksson, I., Rosdahl, I., Seifert, O., Öllinger, K.
- ID
- ZDB-PUB-170712-4
- Date
- 2017
- Source
- British journal of cancer 117(4): 535-544 (Journal)
- Registered Authors
- Keywords
- FAP-α, UV radiation, melanoma, fibroblast, senescence, invasion, cathepsins, TGF-β1
- MeSH Terms
-
- Animals
- Cathepsins/genetics
- Cathepsins/metabolism*
- Cell Line, Tumor
- Cell Movement/drug effects
- Cellular Senescence/genetics
- Coculture Techniques
- Culture Media, Conditioned/pharmacology
- Down-Regulation
- Fibroblasts/drug effects
- Gelatinases/genetics*
- Gelatinases/metabolism*
- Gelatinases/radiation effects
- Gene Expression/radiation effects
- Gene Silencing
- Humans
- Keratinocytes
- Melanocytes
- Melanoma/genetics*
- Melanoma/metabolism*
- Membrane Proteins/genetics*
- Membrane Proteins/metabolism*
- Membrane Proteins/radiation effects
- Neoplasm Transplantation
- Nevus/genetics*
- Primary Cell Culture
- Serine Endopeptidases/genetics*
- Serine Endopeptidases/metabolism*
- Serine Endopeptidases/radiation effects
- Signal Transduction/radiation effects
- Skin/radiation effects
- Skin Neoplasms/genetics*
- Skin Neoplasms/metabolism*
- Skin, Artificial
- Transcriptome
- Transforming Growth Factor beta/antagonists & inhibitors
- Transforming Growth Factor beta/genetics
- Transforming Growth Factor beta/radiation effects
- Ultraviolet Rays*
- Up-Regulation
- Zebrafish
- PubMed
- 28697174 Full text @ Br. J. Cancer
Citation
Wäster, P., Orfanidis, K., Eriksson, I., Rosdahl, I., Seifert, O., Öllinger, K. (2017) UV radiation promotes melanoma dissemination mediated by the sequential reaction axis of cathepsins-TGF-β1-FAP-α. British journal of cancer. 117(4):535-544.
Abstract
Background Ultraviolet radiation (UVR) is the major risk factor for development of malignant melanoma. Fibroblast activation protein (FAP)-α is a serine protease expressed on the surface of activated fibroblasts, promoting tumour invasion through extracellular matrix (ECM) degradation. The signalling mechanism behind the upregulation of FAP-α is not yet completely revealed.
Methods Expression of FAP-α was analysed after UVR exposure in in vitro co-culture systems, gene expression arrays and artificial skin constructs. Cell migration and invasion was studied in relation to cathepsin activity and secretion of transforming growth factor (TGF)-β1.
Results Fibroblast activation protein-α expression was induced by UVR in melanocytes of human skin. The FAP-α expression was regulated by UVR-induced release of TGF-β1 and cathepsin inhibitors prevented such secretion. In melanoma cell culture models and in a xenograft tumour model of zebrafish embryos, FAP-α mediated ECM degradation and facilitated tumour cell dissemination.
Conclusions Our results provide evidence for a sequential reaction axis from UVR via cathepsins, TGF-β1 and FAP-α expression, promoting cancer cell dissemination and melanoma metastatic spread.British Journal of Cancer advance online publication, 11 July 2017; doi:10.1038/bjc.2017.182 www.bjcancer.com.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping